title: Customized high resolution CGH-array for clinical diagnosis reveals additional genomic imbalances in previous well-defined pathological samples.
abstract: High-resolution array comparative genomic hybridization (aCGH) is a powerful molecular cytogenetic tool that is being adopted for diagnostic evaluation of genomic imbalances and study disease mechanisms and pathogenesis. We report on the design and use, of a custom whole-genome oligonucleotide-based array (called KaryoArray®v3.0; Agilent-based 8 × 60 K) for diagnostic setting, which was able to detect new and unexpected rearrangements in 11/63 (~17.5%) of previous known pathological cases associated with known genetic disorders, and in the second step it identified at least one causal genomic imbalance responsible of the phenotype in ~20% of patients with psychomotor development delay and/or intellectual disability. To validate the array, first; we blindly tested 120 samples; 63 genomic imbalances that had previously been detected by karyotyping, FISH and/or MLPA, and 57 sex-matched control samples from healthy individuals; secondly a prospective study of 540 patients with intellectual disabilities, autism spectrum disorder and multiple congenital anomalies were evaluated to confirm the utility of the tool. These data indicate that implementation of array technologies as the first-tier test may reveal that additional genomic imbalances could co-exist in patients with trisomies and classical del/dup syndromes, suggesting that aCGH may also be indicated in these individuals, at least when phenotype does not match completely with genotype.
authors.affiliation: Section of Functional and Structural Genomics of Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain; CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Vallespín
authors.forename: María
authors.initials: M
authors.lastname: Palomares Bralo
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Mori
authors.forename: Rubén
authors.initials: R
authors.lastname: Martín
authors.forename: Sixto
authors.initials: S
authors.lastname: García-Miñaúr
authors.forename: Luis
authors.initials: L
authors.lastname: Fernández
authors.forename: M Luisa
authors.initials: ML
authors.lastname: de Torres
authors.forename: Fe
authors.initials: F
authors.lastname: García-Santiago
authors.forename: Elena
authors.initials: E
authors.lastname: Mansilla
authors.forename: Fernando
authors.initials: F
authors.lastname: Santos
authors.forename: Victoria E
authors.initials: VE
authors.lastname: M-Montaño
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Crespo
authors.forename: Sol
authors.initials: S
authors.lastname: Martín
authors.forename: Victor
authors.initials: V
authors.lastname: Martínez-Glez
authors.forename: Alicia
authors.initials: A
authors.lastname: Delicado
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.forename: Julián
authors.initials: J
authors.lastname: Nevado
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology; D042822:Genomic Instability; D023281:Genomics; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011446:Prospective Studies
keywords: KaryoArray; arrayCGH; chromosomal imbalances; customized array; cytogenetics; microdeletions; microduplications